A wide variety of diseases are characterized by the abnormal accumulation of one or more metabolic products. Such diseases, sometimes referred to as “storage diseases” are typically caused by the increased accumulation of metabolic products (e.g., lipids, proteins, complex carbohydrates, etc.) due to either the inactivity of an enzyme that degrades the products or the hyperactivity of an enzyme that creates the products. Storage disease include but are not limited to glycogen storage disease I, GM1 gangliosidoses, MPS IV B (Morquio B), GM2 gangliosidoses (O, B, AB, B1 variants), Niemann-Pick disease (A, B, and C), Metachromatic leukodystrophy (arylsulfatase A and SAP-1 deficient), Krabbe disease, Fabry disease, Gaucher disease, Farber disease, Wolman disease (cholesterol ester storage disease), MPS I (Hurler and Scheie syndromes), MPS II (Hunter syndrome), MPS III A, C, and D (Sanfilippo A, C, and D), PS III B (Sanfilippo B), MPS IV A (Morquio A), MPS VI (Maroteaux-Lamy syndrome), MPS VII (beta-glucuronidase deficiency), Multiple sulfatase deficiency, Mucolipidosis I (Sialidosis), Mucolipidosis II & III, alpha-Mannosidosis, beta-Mannosidosis, Fucosidosis, Sialic acid storage disease, Galactosialidosis, and Aspartylglucosaminuria Cystinosis.
Historically, storage diseases have been treated by supplementing the “missing” enzymatic activity. Thus, for example, Gaucher's disease can be treated by use of a glucocerebrosidase targeted to spleen cells. Similarly, superoxide dismutase can be targeted to the liver as an anti-oxidant, and so forth.
Such approaches typically have seen limited success. Often the “therapeutic agent” must be specifically targeted to a particular organ or tissue. In addition consistent delivery of the targeted therapeutic agent at physiologically relevant concentrations has proven difficult. In addition, the identification of viable therapeutic agents has proven difficult.